CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants

Bronchopulmonary dysplasia (BPD) remains a major complication and accounts for high morbidity and mortality of preterm infants. The present study aimed to identify the key genes in the development of BPD and to provide some new insights into the pathogenesis of BPD. The {"type":"entrez-geo","attrs":{"text":"GSE108754","term_id":"108754"}}GSE108754 dataset was downloaded from Gene Expression Omnibus database containing 5 samples of BPD patients and 6 of non-BPD infants. The differentially expressed genes (DEGs) between BPD and non-BPD patients were identified by R software. The pathway and function enrichment analyses were performed through Database for Annotation Visualization and Integrated Discovery website. The protein-protein interaction network for DEGs was established by Cytoscape software and the most highly connected module was selected through MCODE plugin. Furthermore, the clinical sample verification among 25 BPD patients and 10 non-BPD infants was carried out in our center. Finally, based on the results above, the gene set enrichment analysis focusing on CD74 upregulated status was employed. Totally, 189 DEGs including 147 upregulated genes and 42 downregulated genes between BPD and non-BPD patients were screened out. The pathway and function enrichments revealed these DEGs were mainly enriched in asthma, intestinal immune network for IgA production, antigen processing and presentation and immune response. Thirteen DEGs (CD74, HLA-DMA, HLA-DRA, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DRB5, HLA-DPA1, HLA-DOA, HLA-DPB1, HLA-DQB2, HLA-DQA2, and HLA-DQB1) were determined as hub genes. The mRNA expression levels of the 13 hub genes were tested by quantitative real-time polymerase chain reaction among our clinical samples. Eventually, CD74 was confirmed to be the most significant highly expressed in BPD samples (P < .001) and its expression level was negatively correlated with gestational age (r = –0.653) and birth weight (r = –0.675). The gene set enrichment analysis results showed the gene sets associated with lupus erythematosus, viral myocarditis, immune network for IgA production, graft versus host disease, cell adhesion molecules and so no were differentially enriched with the phenotype of high-expression CD74. In conclusion, CD74 may serve to predict the BPD development and provide a new therapeutic target for BPD.     

Potential value of PRKDC as a therapeutic target and prognostic biomarker in pan-cancer

Background:While protein kinase, DNA-activated, catalytic subunit (PRKDC) plays an important role in double-strand break repair to retain genomic stability, there is still no pan-cancer analysis based on large clinical information on the relationship between PRKDC and different tumors. For the first time, this research used numerous databases to perform a pan-cancer review for PRKDC to explore the possible mechanism of PRKDC in the etiology and outcomes in various tumors.Methods:PRKDC’s expression profile and prognostic significance in pan-cancer were investigated based on various databases and online platforms, including TIMER2, GEPIA2, cBioPortal, CPTAC, and SangerBox. We applied the TIMER to identified the interlink of PRKDC and the immune infiltration in assorted tumors, and the SangerBox online platform was adopted to find out the relevance between PRKDC and immune checkpoint genes, tumor mutation burden, and microsatellite instability in tumors. GeneMANIA tool was employed to create a protein–protein interaction analysis, gene set enrichment analysis was conducted to performed gene enrichment analysis.Results:Overall, tumor tissue presented a higher degree of PRKDC expression than adjacent normal tissue. Meanwhile, patients with high PRKDC expression have a worse prognosis. PRKDC mutations were present in almost all The Cancer Genome Atlas tumors and might lead to a better survival prognosis. The PRKDC expression level was shown a positive correlation with tumor-infiltrating immune cells. PRKDC high expression cohorts were enriched in “cell cycle” “oocyte meiosis” and “RNA-degradation” signaling pathways.Conclusions:This study revealed the potential value of PRKDC in tumor immunology and as a therapeutic target and prognostic biomarker in pan-cancer.     

Patients with Type 1 Diabetes Treated with Insulin Pumps Need Widely Heterogeneous Basal Rate Profiles Ranging from Negligible to Pronounced Diurnal Variability

Background:Pump-treated patients with type 1 diabetes have widely differing basal insulin infusion profiles. We analyzed consequences of such heterogeneity for glycemic control under fasting conditions.Methods:Data from 339 adult patients with type 1 diabetes on insulin pump therapy undergoing a 24-hour fast (basal rate test) were retrospectively analyzed. Hourly programmed basal insulin infusion rates and plasma glucose concentrations as well as their proportions within, below, or above arbitrarily defined target ranges were assessed for specific periods of the day (eg, 1-7 hours, “dawn” period, 16-19 hours, “dusk” period, reference period 20-1 hours/10-14 hours), by tertiles of a predefined “dawn” index (mean basal insulin infusion rate during the “dawn” divided by the reference periods).Results:The “dawn” index varied interindividually from 0.7 to 4.4. Basal insulin infusion profiles exhibited substantial differences (P = .011), especially overnight. Despite higher insulin infusion rates at 4 and 6.45 hours, patients with the most pronounced “dawn” phenomenon exhibited higher plasma glucose concentrations at those time points (P < .012). Patients with a marked “dawn” phenomenon exhibited a lower probability for low (<4.4 mmol/L) and a higher probability of high values (>7.2 mmol/L) during the dawn period (all P values <.01).Conclusions:We observe substantial interindividual heterogeneity in the “dawn” phenomenon. However, widely different empirically derived basal insulin infusion profiles appear appropriate for individual patients, as indicated by similar plasma glucose concentrations, mainly in the target range, during a 24-hour fasting period.     

CircRNA expression profile and potential role of hsa_circ_0040039 in intervertebral disc degeneration

Purpose:Circular RNAs (circRNAs) play an critical role in the pathological processes associated with IDD. However, the potential roles of circRNAs in IDD remain largely unclear. Here, we identify the circRNAs expression profiles and elucidate the potential role of candidate circRNAs in the pathogenesis of intervertebral disc degeneration (IDD) through microarray data and bioinformatics analyses.Methods:We obtained the datasets of microarrays ({"type":"entrez-geo","attrs":{"text":"GSE67566","term_id":"67566"}}GSE67566 and {"type":"entrez-geo","attrs":{"text":"GSE116726","term_id":"116726"}}GSE116726) from the Gene Expression Omnibus database. The differentially expressed circRNAs and miRNAs were identified using the Limma R package. The target miRNAs and target genes of the candidate circRNAs were predicted using an online tool. Functional enrichment analyses of the target genes were performed using the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed using STRING.Results:A total of 104 differentially expressed circRNAs were identified between the IDD and the control groups, including 41 upregulated circRNAs and 63 downregulated circRNAs (cutoff criteria (|log₂ fold change| > 2, P < .05)). Hsa_circ_0040039, which was the most upregulated circRNA (log₂ fold change = 2.95), was selected for further analysis. The regulatory circRNA-miRNA-mRNA network comprised hsa_circ_0040039, 2 target miRNAs (hsa-miR-424-5p and hsa-miR-15b-5p), and 77 target genes. Functional enrichment analysis showed that the 77 promising target genes are mainly enriched in the ubiquitin proteasome system and Wnt signaling pathway. Further, the PPI network showed that the top 3 hub genes are BRTC, SIAH1, and UBE2V1.Conclusions:A total of 104 differentially expressed circRNAs were identified between the IDD and control groups. Hsa_circ_0040039 may serve as a sponge of hsa-miR-424-5p and hsa-miR-15b-5p, to regulate the expression of downstream genes (such as BRTC, SIAH1, and UBE2V1); thus, it may be involved in IDD-associated pathological processes via the Wnt/β-catenin signaling pathway. Further studies are required to confirm the potential roles of hsa_circ_0040039 in IDD.     

Global trends of researches on bone metastasis: A bibliometric and visualization study

Background:Bone metastasis (BM) has become an important health problem. In recent years, studies on BM are growing rapidly, but there were no bibliometric studies regarding BM. This study aimed to illustrate the overall knowledge structure and development trends of BM.Methods:Research datasets were acquired from the Web of Science database. The time span was defined as “1980–2020”. VOS viewer and Citespace software was provided to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution, H-index status, co-authorship status, and research hotspots were analyzed.Results:Six hundred eighty-two publications met the requirement. USA published most papers (264, 38.7%), and both total citations (13,997) and H-index (57) of USA ranked first. The most productive institution on BM is Amgen Inc. (43). Supportive Care in Cancer (24) published the most papers on BM. “Safety”, “skeletal related event”, “open label”, “management”, “health”, and “prognosis” are the research hotspots in the recent years.Conclusion:In this study, we conduct a systematic and comprehensive analysis on the research in BM field. The publication number was rising in recent years stably. USA contributed mostly not only in quality, but also in quantity. Amgen Inc. published the largest number of articles, Supportive Care in Cancer was the most productive journal related to BM. “Safety”, “skeletal related event”, “open label”, “management”, “health”, and “prognosis” are the research hotspots in recent years. We believe this study can not only show the global research overview in past 40 years but also point the research trend of BM in the future.     

Several critical genes and microRNAs associated with the development of polycystic ovary syndrome

BackgroundWe aimed to identify key genes and microRNAs (miRNAs) associated with the development of polycystic ovary syndrome (PCOS).MethodsGSE84376 mRNA microarray data (15 PCOS granulosa cells and 13 control granulosa cells) and GSE34526 mRNA microarray data (7 PCOS granulosa cells and 3 control granulosa cells) were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA) for differentially expressed mRNAs, and protein–protein interaction (PPI) network analysis were conducted. Next, miRNA-target genes were analyzed and functions predicted, and a competing endogenous RNA (ceRNA) network was constructed. Finally, the relationship between miR-486-5p and PRELID2 was experimentally validated.ResultsSpleen tyrosine kinase (SYK), major histocompatibility complex, class II, DR alpha (HLA-DRA), and interleukin 10 (IL-10) were important nodes in the PPI network. Interestingly, HLA-DRA was significantly enriched in phagosomes mediated by Staphylococcus aureus infection, and in IL-10 enriched during S. aureus infection. One miRNA (miR-486-5p) and a single target gene (PRELID2) were obtained from the ceRNA network. Further experiments showed that miR-486-5p is upregulated and PRELID2 is downregulated in PCOS patient granulosa cells, and that miR-486-5p targets the PRELID2 3′UTR. Topological property analysis showed that hsa-miR-4687-5p downregulation and hsa-miR-4651 upregulation determined the levels of most mRNAs. Levels of the hsa-miR-4651 target gene were significantly enriched in the leukocyte transendothelial migration pathway.ConclusionsOur results suggest that HLA-DRA and IL-10 may contribute to PCOS progression via phagosome enriched by S. aureus infection, while miR-486-5p may be implicated in follicular development in PCOS by targeting PRELID2. Besides, miR-4651 may be involved in inflammation via leukocyte transendothelial migration, by regulating its target gene. These findings may indicate new directions and constitute a breakthrough in studying the pathophysiology of PCOS.     

A randomized,double-blind,placebo-controlled,multicenter clinical trial for efficacy and safety of traditional Chinese medicine combined with antibiotics in the treatment of bacterial pneumonia in children

Background:Pneumonia is the second leading cause of death in children worldwide after preterm birth and certification. Bacteria, viruses, mycoplasma, and other microorganisms are known to be the main causes of pneumonia, of which bacterial pathogenic factors account for 12.5% of cases. The invention and application of antibiotics have improved the prognosis of children with community-acquired bacterial pneumonia (CABP) to a certain extent, but with the emergence of antibiotic resistance worldwide, the mortality of children with CABP is still high. “Maxing Shigan Decoction” and “Qingfei Decoction” have significant efficacy in the treatment of CABP in children, but there is no standardized randomized controlled trial to systematically evaluate the outcomes.Methods:This study is a randomized, double-blind, placebo-controlled, multicenter clinical trial that will randomize 240 patients with CABP to group of Oral Maxing Shigan Decoction, group of Qingfei Decoction or group of placebos administered 3 times a day for 7 days. This study will observe a wide range of clinically relevant endpoints that have been used in clinical trials of pneumonia, including but not limited to clinical cure rate, antibiotic application days, complete antipyretic rate, complete antipyretic days, disease efficacy, traditional Chinese medicine syndrome effect, and antibiotic upgrade treatment rates. Safety will be assessed by monitoring for the incidence of adverse events during the study.Discussion:This clinical trial is the first to evaluate the efficacy and safety of “Maxing Shigan Decoction” and “Qingfei Decoction” in the treatment of children with CABP. The research results will provide a reference for future research design.Trial registration:Chinese Clinical Trial Registry, ChiCTR1900025354. Registered on 14th October 2019-Retrospectively registered, http://www.chictr.org.cn/.     

A narrative review of progress in airway stents

Background and ObjectiveAirway stents, used to restore airway patency, are mostly utilized by patients with malignant airway strictures, and are occasionally used in a range of other airway related diseases, including conditions which result in benign stenosis, malacia, and fistula. There has been an increasing number of airway stents that are being developed thanks to improvements in interventional therapy. However, the method of promoting airway stents for clinical application remains undetermined. Herein, we describe the recent advances in airway stents by reviewing the published studies, providing the reference for clinical decision-making and further research on airway stents.MethodsRelevant articles between January 1964 and November 2021 were obtained from PubMed, Web of Science, and EMBASE databases. The terms “metallic”, “silicone”, “drug-eluting", “biodegradable”, “radioactive”, “three-dimensional (3D)”, and “stents” were searched in different combinations.Key Content and FindingsIn this review, we focus on the latest evidence in terms of the application of various stents with novel materials and designs including novel metallic, novel silicone, drug-eluting, biodegradable, radioactive, and 3D stents for airway stenosis. Despite reducing the well-known complications of all current commercially available stents, novel stents are still in their infancy without a long track record of utility and safety, and remain some limitations. There are more steps to be taken before such stents enter routine clinical practice.ConclusionsA combination of 3D-printing method and biodegradable material may present a promising avenue of solving the existing problems pertaining to “classic” stents and has potential to become the main trend in the future.     

Screening and identification of key genes between liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) by bioinformatic analysis

Background:Liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) are common primary liver cancers worldwide. Liver stem cells have biopotential to differentiate into either hepatocytes and cholangiocytes, the phenotypic overlap between LIHC and CHOL has been acceptable as a continuous liver cancer spectrum. However, few studies directly investigated the underlying molecular mechanisms between LIHC and CHOL.Method:To identify the candidate genes between LIHC and CHOL, three data series including {"type":"entrez-geo","attrs":{"text":"GSE31370","term_id":"31370"}}GSE31370, {"type":"entrez-geo","attrs":{"text":"GSE15765","term_id":"15765"}}GSE15765 and {"type":"entrez-geo","attrs":{"text":"GSE40367","term_id":"40367"}}GSE40367 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape.Results:A total of 171 DEGs were identified, consisting of 49 downregulated genes and 122 upregulated genes. Compared with CHOL, the enriched functions of the DEGs mainly included steroid metabolic process, acute inflammatory response, coagulation. Meanwhile, the pathway of KEGG enrichment analyses showed that the upregulated gene(s) were mainly enriched complement and coagulation cascades, cholesterol metabolism and PPAR signaling pathway, while the downregulated gene(s) were mainly enriched in ECM-receptor interaction, focal adhesion, bile secretion. Similarly, the most significant module was identified and biological process analysis revealed that these genes were mainly enriched in regulation of blood coagulation, acute inflammatory response, complement and coagulation cascades. Finally, two (ITIH2 and APOA2) of 10 hub genes had been screened out to help differential diagnosis.Conclusion:171 DEGs and two (ITIH2 and APOA2) of 10 hub genes identified in the present study help us understand the different molecular mechanisms between LIHC and CHOL, and provide candidate targets for differential diagnosis.     

The profile analysis of circular RNAs in cervical cancer

Cervical cancer (CC) is the third most common cancer among women and has a high mortality rate at the advanced stage. The mechanisms underlying the development and progression of CC are still elusive. Circular RNAs (circRNAs) play an important role in various physiological and pathological processes. The aim of this study was to identify the circRNAs significantly associated with cervical squamous cell carcinoma (CSCC), in order to discover novel diagnostic markers and elucidate their mechanistic basis.The circRNA expression profiles of CSCC and paired para-cancerous cervical tissues was downloaded from the Gene Expression Omnibus. Bioinformatics analysis were used to screen for the differentially expressed circRNAs (DECRs). The expression levels of hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0075341, hsa_circ_0007905, hsa_circ_0031027, hsa_circ_0065898, hsa_circ_0070190, and hsa_circ_0078383 were verified in CC and normal cervical tissues by quantitative real-time PCR.A total of 197 DECRs were identified between the CSCC and normal tissues, including 87 upregulated and 110 downregulated circRNAs. In addition, 37 miRNAs were predicted for the upregulated circRNAs and 39 for the downregulated circRNAs. Functional analysis showed that the DECRs were associated with positive regulation of substrate adhesion-dependent cell spreading, metabolism, positive regulation of GTPase activity, protein regulation, and intercellular adhesion. The MAPK signaling pathway that plays a significant role in the progression of CC, was also enriched. Consistent with the in-silico analysis, hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0007905 were upregulated and hsa_circ_0078383 was downregulated in CC tissues (P < .001), whereas hsa_circ_0075341 (P < .001) and hsa_circ_0031027 (P = .001) showed opposite trends.We identified novel diagnostic and therapeutic biomarkers of CSCC along with the mechanistic basis.     

Identification of microRNA biomarkers in serum of patients at different stages of atrial fibrillation

BackgroundAtrial fibrillation (AF) is a type of cardiac arrhythmia which is caused by irregular electrical activities in the atria.ObjectiveTo identify serum microRNA (miRNA) biomarkers at three durations (duration since diagnosis of AF) of AF.MethodsThis study included 14 patients with AF and 8 healthy subjects. The blood sample was collected from each patient at baseline (time of diagnosis) and 12-month and 24-month follow-up periods. The serum was used for miRNA sequencing. The differentially expressed miRNAs (DEMs) between the 3 AF and control groups were independently compared. The predicted target genes of DEMs were subjected to functional enrichment and protein-protein interaction network analyses. Additionally, the miRNA-target gene networks were constructed for the 3 AF groups and miRNA time series analysis was performed. The expression of several key miRNAs was verified by real-time quantitative polymerase chain reaction (qRT-PCR).ResultsIn total, 28, 22, and 24 DEMs were identified in the baseline, 12-month, and 24-month groups, respectively. miR-483-5p was the common DEM in the 3 AF groups. In the baseline and 12-month groups, the miR-200b-3p and miR-125b-5p target genes were significantly enriched in the Wnt signaling and several cancer-related pathways, respectively. In the 12-month group, the miR-34a-5p target genes were enriched in the cancer-related pathways. In the miRNA-target gene network, miR-34a-5p regulated the highest number of target genes. The time series analysis revealed that 7 miRNAs, which were downregulated in the control group, were upregulated in the AF groups. The qRT-PCR analysis revealed that the 24-month group exhibited a significant upregulation of miR-483-5p (p < 0.05), whereas the baseline group exhibited significant a downregulation of miR-125b-5p (p < 0.05).ConclusionIn patients with AF, miR-125b-5p and miR-483-5p can be potential biomarkers of the baseline and 24-month periods, respectively.     

Twenty-Four Hour Fasting (Basal Rate) Tests to Achieve Custom-Tailored,Hour-by-Hour Basal Insulin Infusion Rates in Patients With Type 1 Diabetes Using Insulin Pumps (CSII)

Background:Twenty-four hour fasting periods are being used to scrutinize basal insulin infusion rates for pump-treated patients with type 1 diabetes.Methods:Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy undergoing a 24-hour fast as a basal rate test were retrospectively analyzed. Hourly programmed basal insulin infusion rates and plasma glucose concentrations within, below, or above arbitrarily defined target ranges were assessed for periods of the day of special interest (eg, 01:00-07:00 am, “dawn” period, 04:00-07:00 pm, and “dusk” period). Statistics: χ²-tests, paired t-tests were used.Results:Basal rates (mean: 0.90 ± 0.02 IU/h) showed circadian variations with peaks corresponding to “dawn” (1.07 ± 0.02 IU/h from 01:00 to 07:00 am) and, less prominently, “dusk” (0.95 ± 0.02 IU/h from 03:00 to 07:00 pm). Individual mean plasma glucose concentrations averaged 6.6 ± 0.1 mmol/L, with 53.1% in the predefined “strict” (4.4-7.2 mmol/L) target range. Interestingly, during the “dawn” period, plasma glucose was significantly higher (by 0.5 ± 0.1 mmol/L [95% confidence interval: 0.3-0.8 mmol/L; P < .0001]) and the odds ratio for hypoglycemia was significantly lower compared to the reference period.Interpretation:Twenty-four hour fasting periods as basal rate tests frequently unravel periods with inappropriate basal insulin infusion rates potentially responsible for fasting hyper- or hypoglycemia. Notably, the higher basal insulin infusion rate found during the “dawn” period seems to be justified and may need to be accentuated.     

Bioinformatics-based identification of key genes and pathways associated with colorectal cancer diagnosis,treatment, and prognosis

Colorectal cancer (CRC) is known to display a high risk of metastasis and recurrence. The main objective of our investigation was to shed more light on CRC pathogenesis by screening CRC datasets for the identification of key genes and signaling pathways, possibly leading to new approaches for the diagnosis and treatment of CRC. We downloaded the colorectal cancer datasets from the Gene Expression Omnibus (GEO) database site. We used GEO2R to screen for differentially expressed genes (DEGs) of which those with a fold change >1 were considered as up-regulated and those with a fold change <-1 were considered as down-regulated on the basis of a P < .05. “Gene ontology (GO)” and “Kyoto Encyclopedia of Genes and Genomes (KEGG)” data were analyzed by the “DAVID” software. The online search tool “STRING” was used to search for interacting genes or proteins and we used Cytoscape (v3.8.0) to generate a PPI network map and to identify key genes. Finally, survival analysis and stage mapping of key genes were performed using “GEPIA” with the aim of elucidating their potential impact on CRC. Our study revealed 120 intersecting genes of which 55 were up- and 65 were downregulated, respectively. GO analysis revealed that these genes were involved in cell proliferation, exosome secretion, G2/M transition, cytosol, protein binding, and protein kinase activity. KEGG pathway analysis showed that these genes were involved in cell cycle and mineral absorption. The Cytoscape PPI map showed 17 nodes and 262 edges, and 10 hub genes were identified by top 10 degrees. Survival analysis demonstrated that the AURKA, CCNB1, and CCNA2 genes were strongly associated with the survival rate of CRC patients. In addition, CCNB1, CCNA2, CDK1, CKS2, MAD2L1, and DLGAP5 could be correlated to pathological CRC staging. In this research, we identified key genes that may explain the molecular mechanism of occurrence and progression of CRC but may also contribute to an improvement in the clinical staging and prognosis of CRC patients.     

Prediction of Individual Basal Rate Profiles From Patient Characteristics in Type 1 Diabetes on Insulin Pump Therapy

Background:Basal rate profiles in patients with type 1 diabetes on insulin pump therapy are subject to enormous inter-individual heterogeneity. Tools to predict basal rates based on clinical characteristics may facilitate insulin pump therapy.Methods:Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy were collected. Basal rate tests were performed over 24 hours. A mathematical algorithm to predict individual basal rate profiles was generated by relating the individual insulin demand to selected clinical characteristics in an exploratory cohort of 170 patients. The predicted insulin pump profiles were validated in a confirmatory cohort of 169 patients.Findings:Basal rates (0.27 ± 0.01 IU.d^−1.kg⁻¹) showed circadian variations with peaks corresponding to the “dawn” and “dusk” phenomena. Age, gender, duration of pump treatment, body-mass-index, HbA_1c, and triacylglycerol concentrations largely predicted the individual basal insulin demand per day (IU/d; exploratory vs prospective cohorts: r² = 0.518, P < .0001). Model-predicted and actual basal insulin rates were not different (exploratory cohort: Δ 0.1 (95% CI −0.9; 1.0 U/d; P = .95; prospective cohort: Δ −0.5 (95% CI −1.5; 0.6 IU/d; P = .46). Similarly, precise predictions were possible for each hour of the day. Actual and predicted “dawn” index correlated significantly in the exploratory but not in the confirmatory cohort.Interpretation:Clinical characteristics predict 52% of the variation in individual basal rate profiles, including their diurnal fluctuations. The multivariate regression model can be used to initiate or optimize insulin pump treatment in patients with type 1 diabetes.     

Association of Systemic Lupus Erythematosus Susceptibility Genes with IgA Nephropathy in a Chinese Cohort

Background and objectives

One hypothesis states that IgA nephropathy (IgAN) is a syndrome with an autoimmune component. Recent studies strongly support the notion of shared genetics between immune-related diseases. This study investigated single-nucleotide polymorphisms (SNPs) reported to be associated with systemic lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in controls.

Design, setting, participants, & measurements

This study investigated whether SNP markers that had been reported to be associated with SLE were also associated with IgAN in a Chinese population. The study cohort consisted of 1194 patients with IgAN and 902 controls enrolled in Peking University First Hospital from 1997 to 2008.

Results

Ninety-six SNPs mapping to 60 SLE loci with reported P values <1×10⁻⁵ were investigated. CFH (P=8.41×10⁻⁶), HLA-DRA (P=4.91×10⁻⁶), HLA-DRB1 (P=9.46×10⁻⁹), PXK (P=3.62×10⁻⁴), BLK (P=9.32×10⁻³), and UBE2L3 (P=4.07×10⁻³) were identified as shared genes between IgAN and SLE. All associations reported herein were corroborated by associations at neighboring SNPs. Many of the alleles that are risk alleles for SLE are protective alleles for IgAN. By analyses of two open independent expression quantitative trait loci (eQTL) databases, correlations between genotypes and corresponding gene expression were observed (P<0.05 in multiple populations), suggesting a cis-eQTL effect. From gene-expression databases, differential expressions of these genes were observed in IgAN. Additive interactions between PXK rs6445961and HLA-DRA rs9501626 (P=1.51×10⁻²), as well as multiplicative interactions between CFH rs6677604 and HLA-DRB1 rs9271366 (P=1.77×10⁻²), and between HLA-DRA rs9501626 and HLA-DRB1 rs9271366 (P=3.23×10⁻²) were observed. Disease risk decreased with accumulation of protective alleles. Network analyses highlighted four pathways: MHC class II antigen presentation, complement regulation, signaling by the B-cell receptor, and ubiquitin/proteasome-dependent degradation.

Conclusion

From this “systems genetics” perspective, these data provide important clues for future studies on pleiotropy in IgAN and lupus nephritis.     

Meta-analysis on aspirin combined with low-molecular-weight heparin for improving the live birth rate in patients with antiphospholipid syndrome and its correlation with d-dimer levels

Background:Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer.Methods:The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The “Risk of Bias Assessment” tool and the “Jadad Scale” provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software.Results:In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22–1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09–1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results.Conclusion:Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants.